Agents inhibiting fungus growth and method of controlling fungi therewith

ABSTRACT

AGENTS FOR INHIBITING THE GROWTH OF FUNGI, WHICH CONTAIN AS ACTIVE COMPONENT 5-AMINO-1,2-DITHIOL-3 ONES SUBSTITUTED AT THE AMINO GROUP AND ALSO IN 4-POSITION, AND METHOD OF CONTROLLING PHYTOPATHOGENIC AND OTHER NOXIOUS FUNGI WITH SUCH AGENTS, WHICH ARE OF SURPRISINGLY LOW PHYTOTOXICITY.

sdssta st 3,659,010 t r AGENTS INHIBITING FUNGUS GROWTH AND METHOD OF CONTROLLING FUNGI THEREWITH I I I v Jorg Bader, Arlesheim, and Karl Gatzi, Basel, Switzerland, assignors to Ciba-Geigy Corporation, Ar'dsley,

No Drawing. Division of application Ser.= No.- 706,614, Feb. 19, 1968, now Patent No. 3,527,867, which is a continuation-jh-part of application Sen No. 621,800, Mar. 9, 1967, which in turn is a continuation-in-part of application Ser. No. 555,994, June 8,1966. This application Apr. 13', 1970',Ser.No.3i2,47 6 Claims priority, application Switzerland, June 11, I965, 8,200/65; Feb. 23, 1967, 2,700/67 Int. Cl. A01n 9/12, 9/22; C07d 71/00 US. (:1. 424-477 4 Claims ABSTRACT OF THE DISCLOSURE Agents for inhibiting the growth of fungi, which contain as active component S-amino-l,2-dithiol-3Fones' substituted at the amino group and also in 4-position, and method of controlling phytop'athogenic and other noxious fungi with such agents, which are of surprisingly low phvtotoxicity.

RELATED APPLICATIONS This application is a division of our co-pending application Ser. No. 706,614, filed Feb. 19, 1968,- now 13.8; Pat. No. 3,527,867. Application Ser. No. 706,614 was a continuation-in-part of our patent application Ser. No. 621,-

800, filed Mar. 9, 1967,. which in turn was a continuationin-part of our application Se'r. No: 555,994, filed June 8, 1966', both now abandoned.

DETAILED DISCLOSURE or agents containing them. It also concernsthematerials' and objects so protected;

Certain representatives from the class of l,2-dithiol- 3-ones, namely 1,2-dithiol-3-ones chlorinated inthe 5"- position such as 4,5-d-ichloro-l,2-dithiol-3 -one (German patent application No. 1,102,174) and 4yaryl-5-chloro- 1,2-dithiol-3-ones (German patent application No. 1,126, 668) have been described inthe literature as pesticidally or fungicidally active substances.

However, those compounds are either, for practical purposes, of insuflicient activity against phytopathogenic fungi and/or their spores, or they are unsuited for use in the control of phytopathogenic fungi due to their e'x-- cessively high phytotoxicity. The antifung'ally active known compounds are especially phytotoXic,- for instance, against such typical plants liable tosuffer from fungalinfestation, beans, cucumbers, and the like.

In contrast thereto, the invention provides antifungal 3,659,010 Patented Apr. 197a agents which contain, as active ingredients, 5-a'rnino-'1, 2 dithiol-3-ones of the formula wherein R represents hydrogen, an alkanoyl or abenzoyl radical or an aliphatic hydrocarbon radical substituted by fiinc tional groups, especially alkyl, hydroxy-alkyl, lower nitroso-p'iperazino, N-lower alkanoyl piperazino', N

lower alkoxycarbonyl-piperazino, N-benzylpiperazino or N-benzoyl-piperazino, and

R represents halogen, a lower alkyl radical or a phenyl radical optionally substituted by lower alkyl, but preferably R represents chlorine,

and which are excellently suitable for combatting in particular phytopathogenic fungi, but also fungi which injure and destroy organic materials other than plants, and objects made of such materials as well as for the protection of such materials and objects from attack by such fungi. The agents according to the invention are very well tolerated by the above-mentioned plants.

Particularly useful on account of their activity against phytopathogenic fungi are those compounds of Formula I in which R represents chlorine or bromine, and preferably the former.

Lower used with an aliphatic radical or moiety in this specification and in the appended claims means that such radical or moiety has from 1 to 4 carbon atoms.

Aliphatic hydrocarbon radicals symbolized by R and R in Formula I, are in particular lower alkyl radicals,- having 1 to 4 carbon atoms, which radicals are unsubstituted or can be substituted by functional groups such as preferably hydrox-y or lower alkoxy, but also by amino, carboxy, carbamoyl, alkylthio, alkylamino, dialkylamino, alkoxycarbonyl' or N-alkyland N,N-dialkyl-carbamoyl groups. One ofthe radicals R or R can alsor'ep'resent a lower alkyl, especially a methyl or ethyl radical substi tuted by the phenyl radical, or it can be a benzoyl' radical; the benzene nucleus of such' phenyl or benzoyl radical can in turn be substituted, especially by alkyl, alkoXy, halogenoalkyl or halogen.

Alkyl in the definitions of substituents, especially groups; furthermore non-ionog'eni'e groups such aslialbg'en atoms, especially chlorine,ibromi'ne or fluorine, carbamoyl,

sulfamoyl, mon ,-or,di-substi tuted, and prefefably inonoo'r di-alkyl substituted carbamoyl or sulfamoyl groups;

alkoxy-carbonyl amino, cyano, nitro or ac 'rgronps uie latter being preferably lower alkanoyl groups; furthermore hydrocarbon radical-s, especially alkyl, alkenyl, aryl or aralkyl radicals, and such radicals linked to the aromatic nucleus, of the phenyl or naphthyl radical, via an oxygen or sulfur or nitrogen atom, in the latter case especially via an imino, preferably an unsubstituted or an alkyl-substituted imino bridge, or via a sulfinyl or sulfonyl bridge; the .last mentionedhydrocarbon radical can in turn be substituted by one or several substituents selected from halogen and the other above-mentioned ionogenic and non-ionogenic substituents. I

These groups do not impair the fungitoxic activity of the compounds of Formula I and do not impart to these compounds a degree of phytotoxicity damaging to cultivated plants to be protected by these compounds.

The heterocyclic radicals represented by R and R Whentakentogether with the 'nitrogenatorn to which they are linlgedcan be monoor poly-substituted, e.'g., by an allryl allroxy, alkoxycarbonyl, N-alkyland N,N-dialkylcarbamoylgaminoalkyl or carbarnoyl group. Alkyl in all ,these groups is preferably lower alkyl.,.

Qptirnal antifungal activity is sho wn by those compounds falling under Formula I in which; =R 'andR are lower allryl, orin which R and R togetherwith the nitrogenatorn form a heterocyclic ring, e.g. piperidino, methyl piperidino, morpholino, or heaamethylen'eimino;

on those. compounds in which R representshydrogen or lower alkyl, R -representsa phenyl radical any substituent of which is selected from hydroxy, a grouping carboxy, sulfo, a grouping R4 soiN Rs a giii ih lower alkoxy carbonyl lower alkanoyl, cyano, nitro, trifluoromethyl, lower al'kyl, lower alkoxy, loweralkylthio, lower alkyl-sulfinyl, benzy'l and'phenyl; eachof R 'and R5 represents .ihdependently hydrogen or lower alkyl; and R represerits-brornine or chlorine, but especially 'the latter.-

The compounds of Formula I contained in the new agents as"active-si1bstances are active against numerous phytopathogenic fungi. The agentsserve to protect-plant's V or parts. theieof "such as blossom, seeds, jtriiit, roots,

stems andfoliagefrom'a'ttack by 'fungi and to combat fungi on these parts of plants.

e.g; Pythium, Fusarium and Rhizoctonia'fungi.

The 5-amino-1,2-dithiol-3-ones of Formula I have good to very good fungistatic activity against fungi such as Zspergillus niger ATCC, Penicillium exp., Fusarium oxysporum, Candida albicans, etc., which injure and destroy organic materials such as wood, leather, synthetic plastics, fabrics, coating agents, etc. They also show bacteriostatic activity.

The marginal concentration inhibiting the growth of these fungus strains is at about 3 to 30 p.p.rn. of active substance. On impregnation with solutions or dispersions of active substance containing at least 1 g. of active substance per liter, the materials treated are given effective and long-lasting protection. I

The compounds of Formula I are produced by reacting a .S-chloro-1,2-dithiol-3-one which is substituted in 4- po s'ition by a substituent as defined under R in Formula I with an amine of the formula HNR R wherein R; and R2 have the same meanings as in Formula Land, if'the basicity of the amine is too low, in the presence of an acid-binding agent, e. g. a tertiary amine such as a trialkylamineor'dialkylan'iline; compound-s falling under Formula I'in which R2 is not hydrogen can be obtained by introducing into the corresponding S-anilinoor S-naphthylamino-1',2 dithiol:3-one which is substituted in 4-po sition by R as defined in Formula I, an aliphatic hydrocarbon radical or an alkanoyl or benzoyl radical, .'e.g. by reaction with a correspondingly constituted alkylating or acylating agent, respectively. If R contains a second reactive group, e.g. a secon'dary'amino group, this may be protected as usual, e.g. by the nitro group, and the protecting group may be Split off thereafter.

The invention is further illustrated by the following noh-iimitative examples. Parts and. percentages given therein are by weight unless expressly stated otherwise. Temperatures are in degrees Centigrade.

EXAMPLE 1 To a suspension ,of 5 parts of 4,5- dichloro-1,2-dithiol- 3-one in 5 parts of ethylene glycol monomethyl ether, 12. mlpof aqueous 30% solution of dimethylamine are added in portionsin the course of 5 minutes. After each addition, the mixture is 'well shaken, and the reaction flask .is cooled with running water. 'After completion of the additiomthe mixture is stirred at 30 for l5 minutes and then "at0 forfa'nother 30 minutes. The crystalline reaction product is filtered 01f, washed withwater, and recrystallized from methanol. Thus are obtained 2.5 parts (48% of the theoretical amount) of 4-chloro-5-dimethylamino-1,2-dithiol-3-one in white crystals of melting point EXAMPLE 2 187 parts of 4,5'-dich loro-l,2-dithiol-3'one are sus pended ihAQOparts of ethanol. To thissuspension, a mixture of 160 parts of pyrrolidine and parts of ethanol is added within 10 minutes with stirring. During the addition the temperature is held at 20-25 by external cooling; Stirring is then continued at room temperature (20") for about '6 hours. Then the crystals are filtered off, washed with 'cold ethanoland water, and recrystallized from2000 parts "of ethanol. There are bbta'iried lZO parts (54% "of the theoretical amount) "of 4 c hloro 5- pyrrolidiiro-l,2 dithiol 3-one. The melting point is 142- 144". EXAMPLE 3 1 87 parts of tj-dichloro-l,2-dithiol-3-one are dissolved 1000, parts of ether, and 370'parts of n-dodecylamine are added, with stirring, insmall-portiods (about 20 parts at a. time) over a period of ca. 30 minutes withis filtered and the filtrate evaporated. The'rerriaining oil is treated with 1000 parts of petrol ether (13.1. 30 50") whereupon the 4-chloro'-5-n-do'decylamino-1,2-dithiol-3- one separates in crystals. It is filtered off and recrystal lized' from diisobutylene (a mixture of 2,4,4-trimethyl-1-- pentene and 2,4,4-trimethyl-2-pentene)'. The purified product melts at 62.

By repeating the above example but using in lieu of n-dodecylamine an equivalent amount of the corresponding amines, there are obtained 4-chloro-5-benzylamino-1,2 dithiol-3-one, M.P. 141 4-chloro-5-methylamino-1,2-dithio1-3-one, M.P. 168.

EXAMPLE 4 187 parts of 4,5-dichloro-1,2-dithiol-3-one are suspended in 800 parts of methanol, and 230 parts of mononitroso-piperaizine (prepared according to US. Pat. No. 2,907,767) are added thereto with stirring in the course of minutes. The 4,5-dichloro-l,2-dithiol-3-one dissolves during the addition, and the reaction product separates in the form of crystals. The thick, greenish magma is stirred for one hour at room temperature. Then the crystals are filered off, washed with 3000 partsof Water, and recrystallized from methyl-Cellosolve. There are obtained 163 parts (61% of the theoretical amount) of 4-chloro-5-(N-nitroso)-piperazino 1,2 dithiol-3-one in fine crystals of melting point 161 EXAMPLE 5 A mixture of 52 parts of 4-chloro-5-(N'-nitroso)-piperazino-1,2-dithiol-3-one, 79 parts of aqueous 36% hydrochloric acid, 23.5 parts of urea, and 25 parts of methyl- Cellosolve is heated at 80-90' with stirring for 150 minutes. Strong fuming is observed at the beginning. The resulting yellow solution is set aside for 12- hours. Then the solvents are removed under reduced pressure, and the white residue is recrystallized from dimethylformamide.

There are obtained 40 parts (78% of the theoretical amount) of 4-chloro-5-piperazino-1,2-dithiol-3-one hydrochloride. The product melts at 235 with decomposition. The free base may be separated from the aqueous solutionof its hydrochloride by the addition of sodium hydrogen canbonate. It crystallizes from ethanol in plates; M.P.. 107.

EXAMPLE 6- remains insoluble. It is washed with a little ethanol, and

recrystallized from methyl-Celll'osolve. point is 156.)

(The melting EXAMPLE 7 By repeating Example 2 but replacing the amine used therein by an equivalent amount of one of the amines given below, there are obtained the correspondingly S-substituted 4-ch1oro-1,2-dithiol-3-ones:

2-hydroxyethyl-amine, di-(2-hydroxyethyl)-amine, 3-methoxy-propylamine, di-(2-methoxy-ethyD-amine, piperidine, hexamethyleneimine, morpholiue, N-methyl-piperazine, N-acetyl-apiperazine, N-ethoxycarbonyl-piperazine, N-benzyl-piperazine, N-benzoyl-piperazine.

By using, in Example 2, 4,5-dibrorno-1,2-dithibl-3-one, produced analogously to the 4,5-d'ichl'oro compound, fromhexa-bromo-propene and sulfur, and' pyrrolidine or'oneof the other amines used in Examples 1 and 3 to 7, there are obtained the correspondingly S substituted 4-brom0- 1,2-dithiol-3-ones.

By using in Example 2, 4rnethyl-5-eh=loro-1,2'-dith'iol 3 one (prepared as described in German patent application- 1,126,668), and pyr-rolidine or one of the other aminesused in Examples 1 and 3 to 7, there are obtained the correspondingly substituted 4-met-hy1-'1,2 dithiol 3-ones.-

EXAMPLE 8' A mixture of 27 parts of N-isopropylaniline, 19"par't s of 4,5-dichloro-1,2-dithiol-3-one and' 12 parts of methanol is heated at 70-80" for about 100 hours; Then, 50 more parts of methanol are added, and the mixture is allowed to cool. On scratchingwith aglass rod, the product crystallizes. It is filtered off and recrystallized from ethanol. There are obtained 19 parts of- 4-chloro5-N-isopropyl anilino-1,2-dithiol-3-one; M.P. 112.5-113 EXAMPLE 9 To a mixture of 16.5 parts of anthranilic' acid ethyl ester, 18.7 parts of 4,5-dichloro-1,2-dithiol-3-one and 100 parts of ethanol, 10.1 parts oftriethylamine are added dropwise with stirring during 15 minutes, the internal temperature of the mixture being kept at 2'0-25 by cooling. Stirring is continued for 5" hours without cooling.

During this time the product separates incrystals. It isfiltered, and washed with ethanol and then with water. After drying, 13.7 parts of 4-chloro-5-(2-ethoxycarbonyl anilino)-1,2-dithiol-3-one, M.P. 142-1481", are obtained. Recrystallization from dioxane' yields 10.7 parts of pure product, M.P. 148.5-151.5.

If in the above example, 10.7 parts of 2,6 -lutidine (2,6- dimethyl-pyridine) are used in lieu of the triethylamine the yield of pure product is 11.5 parts.

EXAMPLE l0 parts of 4-chloro-5-(2 -ethoxycarbonyl-anilino)-1,2- dithiol-S-one are dissolved in a' solutionof 8 parts of sodium in 250 parts of ethanol. To the resulting solution;.- I

40 parts of dimethylsulfate are added in one portion, and

the mixture is set aside for 10 hours at room temperature. On scratching, the product crystallizes. It is filtered 01f, Washed subsequently with ethanol and water and recrystallized from ethanol. The yield of 4'-'chloro'-5"-(N- methyl-2'-ethoxy-carbonyl-aniline)-1,2-dithiol-3-one is 65 parts. The product melts at 101-103 EXAMPLE 1 l To a suspension of 1 87 parts of 4 ,5-dichloro-1,2-dithiol- 3-one in 500 parts of methanol, are added 186 parts of aniline with stirring and cooling during one hour. Stirring is continued for one fil'rther hour Without cooling. The mixture is then refluxed for 12 hours. After cooling, the

crystalline product is filtered oil? and recrystallized from ethylene glycol monomethyl ether (methylcellosolve).

TABLEfCo-ntinued L i. 4 Produced T u .parts of 4fchloro an1lmo 1,2-d1th1ol-3-one, Ex fiiii ig h i iiii M.P. 163-4, are obtained. v No: R1 R1 7 0.) pie N'o.'- V EXAMPLE 13 0 47...- H 4-ethyl-phenyl 105-100 '9 48--.. H 2-hydrox;y-phenyl. 161-162 9 73.2 parts of 4-chloro-5-an1l1no-1,2-d1th10l-3-one are 3.. g... g;- n 1 r qhe u- 145-147 9 dissolved in 300 parts 'of dry pyridine, and 6 3 parts of g gg 'fig 523;? g benzoylchloride, are added dropwise while stirring durlng g ijgg gg -m myl 219 5 338 0 Q i u j a te ra ebeing main- 10 5411;332:1332: t' $th1a5?i% -Zn1- lit-115.5 13 tamed by cooling. Then the mixture 1s allowed to warm 23" g ijs ug a g yfi p l e ngk ing-@2 1 v gredva y wi i fi u Wi 9 r m 57.... Methyl--- 2'-metho xycarbonyl-phenyl. 97-100 0 perature. Thereafter, the mixture 1s added to 1500 parts 2 fi lfi igg g v -mnn 233 9 of ice water. An oily product separates which soon solidi- 6 III: (133.. 1: h 3 ;l%16:fifieny1 124.125 3 fies. It 1s thoroughly ground with 1000 parts of water'and 15 8%" ii-i gi fiS 'p g i 84 13? 10 h ,w gy q q 150 parts e methanoll- 3:: 1133...: wiN giti ii 3 car amoy -p any '1 e um sso ved, crysta lme material 18 twice recrysta 64"" Ham"; ahmmdmethyb u 9 lized,firs t from a mixture of benzene and petrol and then I V ulfamoyl).phenyl frornisopropanol. There are obtained 76.5 parts of 4- H3 fl y 12 chloro-5-N benzoyl-anilino-1,2-dithiol-3-one, MP. 155- 20 66" H yienglzphenylw 9 156; y ij- %-p y 12 I Further tfchloro-1,2 dithiol-3 ones falling under Forsiiinilnifififii mula' I are produced from the correspondingly substituted R reactants in accordance with the procedure described in 1 the example listed in the last column of the following 2r table, these compounds hearing as substituents R and R or as hterqcychc substltuents 7 3I.methy1 piperidino 8O 81 2 R1 71.... 4-methyl-piperidino-. 81-82 2 N/ 1 Decomposition. n

\R 2 By saponifieation of its acetyl compound obtained in Example 12.

. TEST I those shown in the res ective columns of the table. t 1

v p I The antifungal activity of the active substances of For- P mused mula I against spores of phytopathogonic fungi was deter- Memng racrcordmg mined by a germination test on spores of the following Ex. v point to Exam- 5 ecies; a No J, R1 R17 7 v i (0 pleNo.- p A r v V H 14"" pH; gmyamphenyl 1 2524254 9 rnqrla emus. Botrytzs cmerea, Clasterosponum c., r 1' 'th fieny1 155-456 12 Conzo rhyr mm dzpL, Fusarzum culmorum, Mucor spec.,

--do Penicillium spec., S temphylium cons.

9 0 12 1 com. of 1%, 0.1% and 0.01% acetone SOlIltlOl'lOf the 3 active ingredient is placed on each'oftwo glass slides (26- 9 76 mm.) under the same conditions. Thesolvent is evapg orated off and a uniform coating of active ingredient is obtained on the glass slides. The slides are inoculated with 4-,chlorohen l..-.'.' 9 155 spores of the above fungi and then ltept 1n dishes at room ,3Adichlorgphenyl 26%; }8 temperature m an atmosphere which is almost saturated 2emeth lon 29 zumethgxphefwr 122423 10 with steam. After 2 3 and 4-5 days, the germinated spores i n gi, "Hem 117-118 g are counted. 31...- H. 3-t uorome y y I 2 32" gfbthowphenylnu, 1 g The results are summarized in the following table. f f 8 82 12 means an at least inhibition of germinationefg fected by the residue of 1 com. of a 1% acetone solu- 10 tion of active ingredient, i8 means the same effect attained by the residue of l ccm. of a 0.1% acetone solution of the active ingredient, Phenyl 8 means an at least 90% inhibition of germination 42.... 2'-carbamoyl-phenyl 19s 10 attained by the residue of 1 ccm. of a 0.01% acetone ji 1% solution of active ingredient, I 'i'iia i figiliiyiiiiijj"13:""i i4' 0 means no inhibition of germination with the concentra- 'fl- 226427 9 6O tions of active ingredientgiven above.

TABLE I Spore Germination Test Alt. Botr. Clast. Con. 'Fus. Mus. Penis. St. Active substance i I tau. cin. e. di culm. spec. spec. cons l 4-chloro45-dimethylamino-1,2-dithiol-3-one i l -6-dieth lamino-1,2-,dithiol-3-ono p ii ixgigse-u dox ah iammo-i annie-one T l z 4-chloro 5.-pyrrolidino-l,2dithiol-3-one i. LI r wif gr 3 x3 J bl '-5mor o o- 0- one 1 iinl if) JS-hexaiinethyleneiniino-l,2-dithiol-(Mne i..

4,5-dichloro-l,2 dithiol-3-one (German Patent application No. 1,102,174)

TEST II V The activity against phytopathogenic fungi was further tested on (a) beans infested with Uromyces appendiculatus,

(b) cucumbers infested with powdery mildew (Erysiphe cichoracearum),

(c) tomatoes, against Alternmia solanis, causing spotty leaves.

(a) Leaves of bean plants (Phaseolus vulgaris) in the two-leaf stage were sprayed with an aqueous suspension containing 0.1% of active substance.

The suspension is obtained from the 10% wettable powder described as form for application below, by ,diluting with water. After drying, the leaves are infested with a fresh suspension of spores of Uromyces appendiculatus. The plants are then left for one day in a moist room and then kept in a greenhouse. After about 7 to 10 days the test is evaluated.

(b) Cucumber (Cucumis sativus) leaves are treated analogously to the description given under (a), then sprayed with a fresh suspension of spores of powdery mildew (Erysiphe cichoracearum), then kept for one day in a moist room and then placed in a greenhouse. The test results were evaluated after 7 days.

Leaves of 3 to 4-week-old tomato plants (Solanum lycopersicum) were sprayed with an aqueous suspension containing 0.1% of active substance. The suspension was prepared from a 10% spraying powder as described in Example N (d), infra, by dispersion in water.

After drying, the leaves were infested with a fresh suspension of spores of Altenaria salami. The plants were then left for 5 to 6 days in a moist room and then kept in a greenhouse at 20 C. in air having a relative moisture content of 95100%, After about 7 .to 10 days the test results were evaluated.

The known substances 4,5-dichloro-1,2-dithiol-3-one, 4-phenyl-5-chloro-l,2 dithiol-3-one and 4-(p'-tolyl)-5- chloro-1,2-dithiol-3-one (German published patent application No. 1,126,668) were compared with the active substances according to the invention given in the column entitled compounds of the following tables.

The tests were evaluated according to the following scale 10=full activity (no infestation) 91 =decreasing activity O=inactive X=leaves damaged (burned place or zone) XX=up to /3 of the leaf surface damaged XXX=more than /3 of the leaf surface damaged or leaf and plant respectively destroyed.

TABLE IIB Erusiphc Compound cichorac.

4-chloro-5-(N-methyl-an1lino)-1;2edithiol-3-one .10 4-ch10ro-5-(N-methyl-3-chloro-anilino) -1,2-dithio1-3-one 10 4-%hloro-5-(N-methyl:3-trifluoromethylanilino)1,2-d1thio1- 0 -one 1 4-ehloro-5-(N-methyl 2-ethyltanilino)-1,2-dithiol-3-one 7 4-chloro-5-(N-methyl-2'-methyl-anilino)-1,2-dithiol-3-one 10 4-chloro-5-(N-ethyl-anilino) 1,2-dithio1-3-one 10 4,5-dichloro-1,2-dithiol-3-one (disclosed in German Patent application 1,102, 174) 0 TABLE lIC Aliemana Compound ttmus 4-chloro-5-anilino-1,2'dithiol-3-one 10 4-ehloro-5-(4chloro-anilino)-1,2-dithiol-3-one 8 -chloro-fi(4-dimethylamino-anilino) -1,2-dithio1-3-one 10 4-ehloro-5-(N-methyl-3-4-dichloro-anilino)-1,2-dithiol-3-one- 8 4-chl0ro-5-(N-methyl-2-methyl-ani11no) -1,2-dithio1-3-one 9 4-ehloro-5-(N-methy1-2-methoxy-anilino)-1,2-dithiol-3-one.-- 9 4-eh1oro-5-(N-ethyl-anilino) -1,2-dithlol-3-one 8 4-chloro-5-(3-trifluoromethyl-anilino)-1,2-dithio1 3 10 4-chloro-5-(N-benzylanillno)1,2-dithiol 3-one 6 4-chloro-5-(2'-ethoxyanilino) -1,2-d1thiol-3one- 10 4-chloro-5-(2'-methoxycarbonyl-anilino)-1,2-dithi -on -ghloro-fi-(N-methyl-2'-ethoxycarbonylanilino)-1,2-dithi 7 -one 4-chloro-5-(N-methyl-naphth yl-[ll-amino) -1,2-dithio13-one.- 9 4-chloro-5-(N-b enzoyl-anilino) -1,2-dithiol-8-one 8 4,5-dichloro-1,2-dithiol-3-one (disclosed in German Tartan? application 1,102,174)

TEST III 3 parts of an active ingredient as listed in Table.III below are dissolved in 5 parts of a mixture (1:1) of dimethyl formamide and ethylene glycol monomethyl ether. 87 parts of a commercial paint dispersion on polyvinyl acetate-ethyl acrylate copolymer base are stirred in, 5 parts of water are added and the whole is stirred until a homogeneity is attained. Two other solutions are prepared in exactly the same wayexcept that one contains 1 part of active ingredient and 89 parts of the commercial paint dispersion and the other contains 0.3 part of active ingredient and 89.7 parts of dispersion color. In this way, three ready-for-use paints are obtained which contain 3, 1 and 0.3% by weight of active'ingredient, respectively.

The fungistatic and b-acteriostatic activity of these paints is tested by painting therewith pieces of Whatman 3 MM filter paper, and the papers are exposed to the air, first for 3 days at room temperature (20 C.) and then for 8 days at 6 5 C.

TABLE HA I Circular samples of 2 cm. diameter are cut from these 0 nd t z lf y filter papers and each sample is laid with its painted side c c upwards on cultures consisting each of 20 cm. of Mhloro-5-dim8tbY1aminW1;z-qithiol-iflme 10 Sabouraud-Maltose agar inoculated, respectively, with iiiiii3Z3 gfifi iij fifi ifififii:3; ;j Z 2 spores of Pullula ia pullulans 'Paecylomydes varioti, 4-ch1or r m 1 hy g }%g9dg -it- 1 9 Peniczllzum cyclopzum and Candida albzcans. The cultures ififiigigfifi g g,$155,, fig fifgiaggggg zg:- 9 9 are then stored in Petri dishes for 7 days at 28 C. EfiFecone 0 10 tive, broad and prolonged protection agalnst mould formaf g'fg if3?ff izffff fi fl 5 7 tion is achieved on surface painted with the resulting 4-phenyl-5-eh1oro-1,2-dithiol-3-one (known X composition. ffifi2 553: fl ggggg(E55,; X Thefollowing table shows the concentrations of active wmp l uudL 1% XXJg ingredlent with WhlCh mould has formed neither on the compo upper nor on the lower surface of the papers.

TABLE III Effective concentration (percent) Pullu- Paecylo- Penicilmydes lium Candida Compound varioti cyclopium albica'ns 4-chloro-5-dimethylamino-1,2-d1thiol-3-one 3 1 1 4--chlor0-5-1: yrtol1dino-1,2-d1thiol'3-one 1 1 3 -ehlorofi-piperldinod,2-d1thiol-3-one 3 1 3 4-ch1oro-5-hexamethyleneimino-1,2dlthiol-3-one 1 1 1 4-chloro-5-morpholino-1,2-dithiob3-one 1 1 g 0. 3 4-phenyl-5-chloro-1,2-dithlol-3-one (German Patent 1,126,668).... 3 3 3 4,5-dichloro-1,2-dlthlol-3-one (German Patent 1,102, 174) 3 3 3 TESTS IV-(M-(e) 25 g. of -the "active substance to be tested are dissolved in 1 liter of ethylene glycol monomethyl ether. Strips of cotton 'fabric (weight of .1 square meter=about 85 g.) which has been washed at the boil are dipped in this solution and thenma'ngle'd to "40% by weigh t'liquor content. The concentration of active .substanceon vthe fabric is thus 1% by weight. The strips of fabri'c'arehung for minutes in circulating :steamyand'drie dt The strips of fabric are then Washed "twice at 40 for 15 minutes each time with 5 g. of soap per liter of water, rinsed twice with cold water for 3 minutes each time and dried. The eiiectiveness of this treatment was determined by the following tests:

.(a) Inhibition test The inoculated dishes -containingstrains A and B are stored for 24'hou rs at 37, and strain Ciford days at 28. i

' f (b) Maceration test Circulafsamp'les of 46m. diar'neter are cut from the a fabric treated-as-decsribed above, and subjected to maceration in compost'consisting of 50 of cow dung, 30% of compost and 20% of sand. The earth has 30% humidity and is kept at 28 C. After days, the samples are disinterred, cleaned and conditioned. The tensile strength after maceration, measured by-"the resistance to perforatidn is compared with that of the fabric before the treatmentsabove described, the initial" tensile strength having been previously determined. It is expressed in percentage of said initial" tensileustrength. i

g (c)"Moldy spot test (Sireular samples of 8 cm.- diameter are cut from the fabric treated as described above and, placedon sterile Worth --agar plates produced in the following way: Amounts of mb each-ofWorth agar-(Difco Manual, 9th--,editi'on,{p. -244)-arespread iin Petri', dishes. of ill cm. diameter and left to solidify.

. The samples'are-placedon the agar-which is then inoculated with; a'tsporesuspension containing a mixture1of thespores of the fungi Chaetomiumggl obosum, Aspergillus niger and-Trichoderma virido.

The Petri dishes; are; stored for '5- days the growth of mould is then determined.

" TEST "R1ESULTS .(a). Inhibition test 7 +Bacterial andior fungus growth on the upper'and'lower side'of 'thetest sample Sajrriple remains'free from growth ('A)"iStaphylococcus'izureus SG 5 ll (BYCaizdidqdlbiadw (C) -A sperilius' higer (b) Maceration test Final resistance to perforation (in percent).

(c) Moldy spot test +=Moldy spots and growth of mold ="Freefr0nrmo1dy' spots and mold growth at 228" C. and

, Macor- .Moldy -ation spot Compound test :test

i-chloro-fiepip'eridinorlfl-dithioldbne 100 4-phenyl-5-ehloro-l,Z-dithiol-S-one (German Patent For the purpose of protecting organic materials and plants which'may'su'ifer from attack, the active substances can also be 'applied in combination with other substances suitable for the protection of materials or "plants. The antifungally active agents according to the invention are produced in the known ways by intimately mixing and milling the active'substances of general Formula I with suitable carriers, optionally'with the addition of dispers ing 'agentsor'solvents which are inert to the "active sub-' stances. These 'agents'can be in the following forms for application:

Solid forms: dusts, sprinkling-agents, granulates such as coated granules, impregnated granules, homogeneous granules,

Water dispersible concentrates of:active substances: wettable powders, pastes,1emulsions,

Liquidforms: solutions.

To produce 'the solid forms for use (dusts, sprinkling agents, 'gr'anulates) the active substances are mixed with solid'carriers. Examples of carriers are kalon, talcum, bole, loess; chalk, limestone, ground limestone, 'ataclay, dolomite, diatomaceous earth, precipitatedsilicic acid, alkaline earth'silicates, sodium and potassium aluminium silicates (feldspar and mica), calciumand magnesium sulphates, magnesium oxide, milled syntheticplastics, fertilizers such as ammonium sulphate, ammonium phosphate, ammonium nitrate, urea, ground-vegetable-products such as bran,'bark dust, sawdustyground nutshells, cellulose powder, residues ofplant extractions,- active charcoaletc. These carrierscan be-used alone or admixed witheach other.

The'particle size of the carriers is; for dusts up to about IUD/1., for sprinklingagents from about'75 -0.2=mm; and for= granulates from 0.2 -mm.-l rnrn.or coarser.

As a general rule, the concentrations of active substances in the solid preparations is. from 05-80%.

ChemicalDivAWyand'otte, Mich.)], polyvinyl pyrroliidol-lies polyvinylialcohols [c.g. the product sold under 7 "the' commercial name Moviol (Farbwerke Hoechst 1 A..G.,' Frankfurt a. M.)], condensation products of urea- To these mixtures can also bezadded. additives which stabilise the active substance and/or non-ionogenic, anionically and cationically active substances:which,, for example, improve the adhesion of the active substances I on plants and parts of plants (glues and adhesives) and/or (.Carbowaxes), fatty alcohol polyethylene glycol ethers having to 2D ethylene'oxide' radicals per moieculeand 8-18 carbon atoms in fatty alcohol moiety [e. g., the prod- -uctssold-under the commercial names Genapol (Farbwerke Hoechst A. G. Frankfurt a. M.)], condensation products of ethylene oxide/propylene oxide [c.g. the products sold under. the commercial names Pluronics" (produced by Wyandotte Chemicals Corp., Industrial formaldehyde and also latex products.

The concentrates of active substance which can be dispersed in water (wettable powders), pastes and emulsion concentrates, are agents which can be diluted with water to any concentration desired. They consist of active substance, carrier, optionally additives which stabilise the active substance, surface active substances, and anti-foam agents and, optionally, solvents. The concentration of active substance in these agents is 80%.

Wettable powders and pastes are obtained by mixing and milling the active substances with dispersing agents and pulverulent carriers in suitable mixers and milling machines until homogeneity is attained. Carriers are, for example, those mentioned in the paragraph dealing with solid forms for application. In some cases it is advantageous to use mixtures of different carriers. As dispersing agents can be used, for example: condensation products of sulphonated naphthalene and sulphonated naphthalene derivatives with formaldehyde [e.g. the product sold under the commercial name Sellasol (producer I. R. Geigy A.G. Basel)], condensation products of naphthalene or of naphthalene sulphonic acids with phenol and formaldehyde [c.g. the products sold under the commercial name 'Irgatan (producer I. R. Geigy A.G. Basel)], also alkali, ammonium and alkaline earth salts of lignin sulphonic acid, also alkylaryl sulphonates, alkali and alkaline earth salts of dibutyl naphthalene sulphonic acid, fatty alcohol sulphates such as salts of sulphated hexadecanols, heptadecanols, octadecanols, octadecenols and salts of sulphated fatty alcohol polyglycol ethers [e.g., the products sold under the commercial name Eriopon (producer I. R. Geigy A.G. Basel)], this sodium salt of oleoyl ethionate, the sodium salt of oleoyl methyltauride [the products sold under the commercial name Arkopon (producer Farbwerke Hoechst, Frankfurt a.M.)], ditertiary acetylene glycols [c.g. the products sold under the commercial name Surfynol (producer Air Reduction Chemical Company, New York, N.Y.)], dialkyldilauryl ammonium chloride [the product sold under the commercial name Aliquat (producer General Mills Inc., Kankakee, Ill. and fatty acid alkali and alkaline earth salts.

Silicones, Antifoam A, etc., are used, for example, as anti-foaming agents.

The active substances are so mixed, milled, sieved and strained with the additives mentioned above that the solid particle size in wettable powders is 40,u and in pastes is not more than 3a. To produce emulsion concentrates and pastes, dispersing agents such as those given in the previous paragraphs, organic solvents and water are used. Examples of solvents are as follows: alcohols, benzene, xylenes, toluene, dimethyl sulphoxide and mineral oil fractions boiling between 120 and 350. The solvents must be almost without smell, not phytotoxic, inert to the active substances and not easily inflammable.

In addition, the agents according to the invention can be applied in the form of solutions. For this purpose the active substance or several active substances of general Formula I are dissolved in suitable organic solvents, mixtures of solvents or in water. Aliphatic and aromatic hydrocarbons, chlorinated derivatives thereof, alkyl naphthalenes, alone or mixed with each other can be used as organic solvents. The solutions contain the active substances in a cocentration from l-20%.

The agents according to the invention described can be mixed with other bioeidally active compounds or agents. Thus, to broaden the range of action, the new agents can contain e.g. insecticides, other fungistatics, bactericides, fungicides, bacteriostatics or nematocides in addition to the compounds mentioned of general-Formula I. The agents according to the invention can also contain fertilisers, trace elements etc.

The following forms for application of such agents serve to illustrate the present invention further; where not otherwise expressly stated, parts and percentages are given by weight.

'14 EXAMPLE I Dusts To produce (a) a 10% and (b) a 2% dust, the components given below are used:

10 partsof 4-chloro-5-dimethylamino-1,2-dithiol-3:one, 5 parts of highly dispersed silica, parts of talcum.

e 2 parts of 4-chloro-5-hexamethyleneimino-l,2-dithiol-3- one, 1 part of highly dispersed silica, 97 parts of talcum.

The above carriers are intimately mixed and milled with the active substances. The fungicidal dusts so obtained serve for the treatment of seed beds or for dusting plants.

Similarly active dusts are obtained by using in the above compositions in lieu of the active substances mentioned therein, identical amounts of (c) 4-chloro-5-(N-methyl-anilino)-1,2-dithiol-3-one or (d) 4-chloro-5-(3'-nitro-anilino)-1,2-dithiol-3-one.

EXAMPLE II Seed dressing 1 part of liquid parafiin, 24 parts of talcum.

are used to produce (a) a 10% and (b) a 60% seed dress-.

ing.

The active substances mentioned are intimately mixed and then milled with the carriers given and the paraflin as distributing agent. The pulverulent dressings obtained serve for the treatment of seeds of all types.

Seed dressings are also obtained by using in the above compositions in lieu of the active substances mentioned above:

(c) 4-chloro-5-(N-methyl 3 trifluoromethyl-anilino)- 1,2-dithiol-3-one, or (d) 4-chloro-5-(N-ethyl-anilino -1,2-dithiol-3-one.

EXAMPLE III Granulates To produce (a) a 2.5%, and (b) a 5% granulate, the following components are used:

2.5 parts of 4-chloro-5-(N-ethoxycarbonyl)-piperazin0- 1,2-dithiol-3-one, 2.5 parts of kieselguhr, 5 parts of polyethylene glycol, 89.3 parts of ground limestone (0.4-0.8 mm. diameter), 0.7 part of silica.

5 parts of 4-ch1oro-5- 9-hydroxyethylamino-1,2-dithiol-3- one,

1.5 parts of kieselguhr,

0.5 part of cetyl polyglycol ether,

87 parts of ground limestone,

5 parts of polyethylene glycol,

l part of silica.

15 parts of kieselguhr 20 parts of kaolin.

The ground limestone in each formulation is impregnated with the polyethyleneglycol or the cetyl polyglycol ether and then mixed with a mixture of the active substance mentioned, the kieselguhr and silicic acid. These granulates are particularly suitable for-the disinfection of seed beds.

Granulates are also vobtained by replacing the active components in the above compositions by identical amounts of v (c) 4 chloro-S-(N-methyI Zfgmethyl-anilino)-1,2-dithiolne, or (d) 4 chloro-- (N-isopropyl-anilino -1 ,2-dithiol-3-one.

EXAMPLE ,IV

Wettable powders To produce (a) a 25%, (b) and (c) 50% and (d) a wettable powder, the following components are used: i

25 parts of 4-chloro-5-morpholino-1,2-dithiol-3 one 25 parts of kieselguhr I V 2 parts of'hexadecyl glycol ether sulphate 1 part of sodium lauryl sulphate 7 parts of sodium lignin sulphate 40 parts of kaolin.

50 parts of 4-chloro-5-(N'-methyl)-piperazino-1,2-

,dithiol-3 -one 3 parts of oleyl methyl tauride sodiumsalt 2 parts of sodium lauryl sulphate 5 parts of sodium lignin sulphate 2 parts of kaolin/ polyvinyl alcohol mixture (1:1)

38 parts of silic acid (precipitated).

50 parts of 4-chioro-5-pyrrolidino-1,2 dithiole3-one 10 parts of sodium lignin sulphate H 5, parts, of dibutyl naphthalenesulphonicacid sodium salt 10 parts of 4-phenyl-5-morpholino-1,2-dithiol 3-one 10 parts of sodium lignin sulphate 2 parts of a finely milled mixture of kaolin and polyvinyl alcohol (1:1)

10 parts of kieselguhr 38 parts ofkaolin 30 parts of Champagne chalk.

EXAMPLE V v Emulsion concentrates To produce (a) a 5%, (b) andl( c),"a emulsion concentrate, the following components are used:

5 parts ofl4 chloro .5 (N- ethoxycarbonyl) piperazine- 1, 2-,dithiol -3'-oi1e 40 parts of dimethyl formamide .50 parts of petroleum (boiling range 230-270 5 parts of composite emulsifier consisting of the Ca salt or dodecylbenzene sulphonic acid and a condensation product of ethylene oxide andricinus voil (e.g. Emullat I WK, Union Chimique Beige, S.A. Brussels).

10 parts of 4-chloro j-benzylamino-l,Z-dithiol-3 one 35 parts of diinethyl formamide SOpartsof petroleumtboiling range 230270) 5 parts of composite emulsifier consisting of the Ca salt of dodecylbenzene sulphonic acid and a condensation product of ethylene oxide and recinus oil (e.g., Emullat WK, Union Chimique, S.A., Brussels 15 parts of 4-chloro-5 piperidino-l,2-dithiol-3-one 27 parts of dimethyl formamide N 53 parts of petroleum (boilingrange 230-270") 5 parts of composite emulsifyer consisting of the Ca salt "of dodecylbenz ene sulphonic acid and a condensation product of ethylene, oxide and ricinus oil =(e.g. Emullat WK, Union Qhimique S.A., Brussels) The active ingredient used is dissolved in petroleum or dimetliyl formamide and the composite emulsifier is added tovthis solutionf Emulsion concentrates are obtained which can be diluted with water-to any concentration desired. Euch emulsions are suitable for the treatment of cultivatedplants'and also for the impregnation of organic materials such as textiles, wood, leather, syntheticplastics etc.

Emulsion concentrates are also obtained by replacing the active components in the above concentrates by'identical amounts'ot (d) 4-chloro-5-(N-ethyl-2-methoxy-anilino)-1,2-

di tl, i ol- 3,-one, h (e) 4-ch10 ro-5-(N-benzyl-anilino)-1,2rdithiol-3-one, or

(f) 4-chloro-5-Q2'rmethoxy anilino)-1,2-dithiol-3 one.

.We claim:

:1. A. fungal growth-inhibiting, composition comprising at least about 0.01%, calculated on the total weight of the composition, of a compound of the formula wherein R and- ,R taken; together with the nitrogen atom to ,which they are linked, represents hexylmethyleneimino, and

4 R represents chlorine, bromine and. a carrien therefor.

'2. A compositionas defined in claim 1, wherein,

R represents bromine or chlorine.

3. A composition as defined in claim 2, wherein said compoundis 4-chloro-S-hexarnethyleneimino-1,2edithiol- 3-one.

.-4.-The method of inhibiting fungus growth, which, comprises exposing fungi to a fungitoxic amount of a compound of the formula or lower allryl,

17 wherein 3,109,772 R and R taken together With the nitrogen atom to 3,527,867 which they are linked, represent hexamethyleneirnino, 3,546,235 and 5 R represents chlonne, bromme or lower alkyl. 1,102,174 1,126,668 References Clted 1,492,969 UNITED STATES PATENTS 1,528,170 3,031,372 4/1962 Brack 424277 10 3,062,833 11/1962 Boberg et a1. 260327 FOREIGN PATENTS Germany. Germany. France. France.

SH-EP K. ROSE, Primary Examiner 

